Biomarkers for monitoring clinical efficacy of allergen immunotherapy for allergic rhinoconjunctivitis and allergic asthma: an EAACI Position Paper

Allergy. 2017 Aug;72(8):1156-1173. doi: 10.1111/all.13138. Epub 2017 Apr 6.

Abstract

Background: Allergen immunotherapy (AIT) is an effective treatment for allergic rhinoconjunctivitis (AR) with or without asthma. It is important to note that due to the complex interaction between patient, allergy triggers, symptomatology and vaccines used for AIT, some patients do not respond optimally to the treatment. Furthermore, there are no validated or generally accepted candidate biomarkers that are predictive of the clinical response to AIT. Clinical management of patients receiving AIT and efficacy in randomised controlled trials for drug development could be enhanced by predictive biomarkers.

Method: The EAACI taskforce reviewed all candidate biomarkers used in clinical trials of AR patients with/without asthma in a literature review. Biomarkers were grouped into seven domains: (i) IgE (total IgE, specific IgE and sIgE/Total IgE ratio), (ii) IgG-subclasses (sIgG1, sIgG4 including SIgE/IgG4 ratio), (iii) Serum inhibitory activity for IgE (IgE-FAB and IgE-BF), (iv) Basophil activation, (v) Cytokines and Chemokines, (vi) Cellular markers (T regulatory cells, B regulatory cells and dendritic cells) and (vii) In vivo biomarkers (including provocation tests?).

Results: All biomarkers were reviewed in the light of their potential advantages as well as their respective drawbacks. Unmet needs and specific recommendations on all seven domains were addressed.

Conclusions: It is recommended to explore the use of allergen-specific IgG4 as a biomarker for compliance. sIgE/tIgE and IgE-FAB are considered as potential surrogate candidate biomarkers. Cytokine/chemokines and cellular reponses provided insight into the mechanisms of AIT. More studies for confirmation and interpretation of the possible association with the clinical response to AIT are needed.

Keywords: IgE-FAB; IgG4; allergen immunotherapy; basophil activation; biomarkers.

MeSH terms

  • Allergens / immunology
  • Asthma / diagnosis*
  • Asthma / immunology
  • Asthma / therapy*
  • Basophils / immunology
  • Basophils / metabolism
  • Biomarkers
  • Conjunctivitis, Allergic / diagnosis*
  • Conjunctivitis, Allergic / immunology
  • Conjunctivitis, Allergic / therapy*
  • Cytokines / metabolism
  • Desensitization, Immunologic* / methods
  • Humans
  • Immunoglobulin E / immunology
  • Immunoglobulin G / immunology
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / metabolism
  • Prognosis
  • Rhinitis, Allergic / diagnosis*
  • Rhinitis, Allergic / immunology
  • Rhinitis, Allergic / therapy*
  • Treatment Outcome

Substances

  • Allergens
  • Biomarkers
  • Cytokines
  • Immunoglobulin G
  • Immunoglobulin E